Radioisotope generator

ABSTRACT

A generator is provided for eluting a daughter radioisotope from a parent radioisotope. The generator is characterized by an elongate closed vessel having a convergent closed lower end and containing therein a supply of a parent radioisotope material spaced from the closed lower end. The vessel is closed at its upper end with a closure through which extends a first conduit communicating with the upper end of the vessel for introducing an eluant into the vessel. Also extending through the closure is a second conduit communicating with the lower end of the vessel which provides for passage of eluate from the lower end of the vessel.

Holgate et al.

Jan. 9, 1973 [75] Inventors: Richard L. Holgate, Creve Coeur; James R. Montgomery, St. Louis County, both of Mo.

[73] Assignee: Mallinckrodt Chemical Works, St.

Louis, Mo.

[22] Filed: May 25, 1970 [21] Appl. No.: 40,944

[52] U.S. Cl ..250/106 S [51] Int. Cl. ..G2lh 5/00 [58] Field of Search.250/l06 T, 106 SC, 106 R, 106

[56] References Cited UNITED STATES PATENTS 3,564,256 2/1971 Arlman et al. ..250/i08 R X I55 ha;

RADIOISOTOPE GENERATOR ISI BI L V I47 I95 7| 5 U :25 *zai';

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Primary Examiner-James W. Lawrence Assistant ExaminerDavis L. Willis Attorney-Koenig, Senniger, Powers and Leavitt [57] ABSTRACT A generator is provided for eluting a daughter radioisotope from a parent radioisotope. The generator is characterized by an elongate closed vessel having a convergent closed lower end and containing therein a supply of a parent radioisotope material spaced from the closed lower end. The vessel is closed at its upper end with a closure through which extends a first conduit communicating with the upper end of the vessel for introducing an eluant into the vessel. Also extending through the closure is a second conduit communicating with the lower end of the vessel which provides for passage of eluate from the lower end of the vessel.

2 Claims, 8 Drawing Figures lZi I mi

PATENTEDJAH 9 I975 SHEET 2 [1F 4 PATENTEUJMI 9 I973 3,710.1 18

' sum 3 or 4 FIGS FIG.4

PAIENTED JIII 9 I975 SHEET '4 [IF 4 RADIOISOTOPE GENERATOR BACKGROUND OF THE INVENTION This invention relates to the generation of radioactive isotope solutions and more particularly to an improved generator for the generation of a daughter radioisotope from a parent radioisotope.

The invention is particularly concerned with the preparation in a sterile closed system of a solution of a daughter radioisotope, such as technetium-99m, generated from a parent radioisotope, such as molybdenum-99. Conventionally, the preparation of a daughter radioisotope from a parent radioisotope has been carried out using a generator containing the parent radioisotope and an anion exchange medium or other medium, such as alumina, having a high adsorptive capacity for the parent radioisotope but a low adsorptive capacity for the daughter radioisotope. The desired daughter radioisotope is eluted by washing with a suitable solvent or eluant such as a sterile, pyrogenfree isotonic saline solution. The resulting eluate containing the daughter radioisotope in the form of a dissolved salt is useful as a diagnostic agent, for example, and is adapted for intravenous administration.

The generator containing the parent radioisotope adsorption medium for eluting the daughter radioisotope is frequently referred to in the art as a cow, and the elution of the daughter radioisotope therefrom is generally referred to in the art as milking the cow".

Some widely used daughter radioisotopes used in medical diagnosis have relatively short half-lives, e.g., 6 hours, and it is important therefore that they be generated or prepared shortly before usage in the hospital, clinic or other place of use. Thus, there is need, for example, for apparatus enabling generation and containerization under sterile conditions once a day in a hospital or clinic of the eluate, also under conditions wherein the user of the apparatus is afforded maximum protection against radioactive emission from the generator. Prior apparatus for the purpose, such as disclosedin U.S. Pat. Nos. 2,942,943, 3,369,121 and in the copending coassigned U.S. Pat. application of Donald J. Shumate, Ser. No. 658,872, filed Aug. 7, I967, now U.S. Pat. No. 3,535,085 entitled Closed System Generation and Containerization of Radioisotopes, has not been wholly satisfactory, primarily on account of the necessity for carrying out a number of hand operations while the shield for the generator is open, thus exposing the hands and possibly other parts of the operator to radiation. Since the decay characteristics of most of the parent-daughter radioisotope combinations presently in large-scale use require that the generator (the cow") be milked daily, the use of the above prior devices undesirably involves daily exposure of the operator to radioactivity during the milking" operation.

The most widely used prior art generators are of the column type which generally consist of a glass tube closed at both ends with rubber stoppers or closures. In addition to the amount of handling involved in the use of such generators, the necessity for rubber closures or seals at both ends of the tube increases the possibility of fluid leaking, especially with respect to the lower end closure, and therefore decreases the reliability of such generators.

SUMMARY OF THE INVENTION Among the objects of the invention may be mentioned the provision of an improved generator for the generation of a daughter radioisotope from a parent radioisotope; the provision of such a generator which is less subject to leaks occurring at the single closure therefor; and the provision of a generator of this type which may be used in connection with either a pressure system or a vacuum system. Other objects will be in part apparent and in part pointed out hereinafter.

The present invention is thus directed to a generator for eluting a daughter radioisotope from a parent radioisotope comprising an elongate closed vessel having a convergent closed lower end and containing therein a supply of a parent radioisotope, means in the vessel spaced from the lower end thereof for maintaining the supply of the parent radioisotope spaced from the lower end, a closure for the upper end of the vessel, a first conduit extending through the closure and communicating with the upper end of the vessel for introducing an eluant into the vessel and a second conduit extending through the closure and said means and communicating with the lower end of the vessel for passage of eluate from the lower end of the vessel.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective of an apparatus with a generator made in accordance with this invention, a plastic case of the apparatus being illustrated as transparent for viewing interior detail;

. FIG. 2 is a plan ofthe FIG. 1 apparatus;

FIG. 3 is a view in elevation of the apparatus, showing a container in position for receiving the eluate eluted from the generator of the invention in the case;

FIG. 4 is a vertical section on line 4-4 of FIG. 2;

FIG. 5 is a vertical section on line 5-5 of FIG. 2;

FIG. 6 is a horizontal section on line 6-6 of FIG. 3;

FIG. 7 is an enlarged fragment of FIG. 4 showing a plunger and tubular needle of the apparatus driven downward with the needle pierced through the stopper of the container", and

FIG. 8 is an enlarged vertical section of the generator or cow of the invention.

Corresponding reference characters indicate corresponding parts throughout the several views of the drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The generator according to the instant invention shall be described in connection with the total apparatus system for eluting a sterile daughter radioisotope from a parent radioisotope and containerizing the resultant eluate in an evacuated container, as disclosed in the copending and coassigned application of James R. Montgomery and Lloyd G. Struttman, Ser. No. 779,793, filed Nov. 29, 1968, now U.S. Pat No. 3,655,981 dated Apr. 11, 1972. However, it should be understood that the generator of the invention is not limited to use in such apparatus and can be used in various other total apparatus systems.

Referring to the drawings, a generator or cow 1 of the invention is shown as containing a sterile pyrogenfree supply 3 of a parent radioisotope. The generator is enclosed in a shield 5 for shielding the user of the apparatus against radioactive emission from the generator. At 7 is indicated means for holding a sterile pyrogen-free supply of an eluant with the eluant under atmospheric pressure. An eluant conduit 9 extends from means 7 through the shield and into the generator.

At 11 is indicated a tubular fitting adapted for attachment thereto at one end (its lower end) of a tubular needle 13, which may be a conventional hypodermic needle. The apparatus shown, as will ap pear, provides for the sealed sterile containerization of a sterile pyrogen-free eluate eluted'from the parent radioisotope in a sealed sterile evacuated container or vial 15, shown as comprising a glass bottle having a neck 17 sealed at its upper end by a closure 19 adapted to be pierced by the needle 13. Closure 19 may be a conventional rubber stopper, and is shown as having an aluminum foil cover 21. This cover has a removable circular central section, shown removed in FIGS. 1 and 7 leaving an opening 23 in the cover.

Means generally designated 25 is provided for mounting the tubular fitting l1 (and needle 13) for movement away from the retracted position of PK]. 3 in the direction of length of the needle to cause the needle to pierce the closure or stopper 19. An eluate conduit 27 extends from the generator through the shield and has a flexible tubing portion 29 connected to the other end (the upper end) of the tubular fitting 11 permitting the stated movement of the fitting. At 31 is indicated means associated with the fitting 11 for effecting closure of the eluate conduit when the fitting is in its retracted position and opening of the eluate conduit when the fitting is moved downward to cause the needle 13 to pierce the stopper 19 of the evacuated container 15, with resultant suctioning of eluant from the eluant supply means 7 into the generator 1 for eluting a daughter radioisotope from the parent radioisotope in the generator and suctioning of the resultant eluate from the generator through the eluate conduit 27, fitting 11 and needle 13 into the evacuated container 15.

Thegenerator l, as shown, comprises an elongate cylindric vessel 33 constituted by a glass tube resembling a test tube having an integral convergent closed lower end 35 of hemispherical form and a neck 37 at its upper end. A pierceable closure constituted by a rubber stopper 39 is plugged in the neck to seal the vessel. This has an aluminum foil cover 41 from which a circular central section has been removed. A fritted glass filter 43 is mounted in the vessel just above its hemispherical lower end. The vessel 33 is necked down as indicated at 45, and the filter is lodged in the necked-down portion and bonded therein. The space below the filter constitutes an eluate chamber 49, and the filter serves as means for maintaining the supply 3 of the parent radioisotope spaced from the lower end of the vessel, so that chamber 49 is maintained free of'the supply 3.

The filter 43 has a center hole 51. The eluate conduit 27 comprises a length of relatively small diameter metal tubing 53 (e.g., stainless steel tubing) bent to have a vertical leg 55 and a horizontal arm 57. The lower end of the vertical leg 55 is beveled as indicated at 59. The vertical leg 55 extends down through the stopper 39, its beveled lower end 59, permitting it to be pierced through the stopper, and reaches down through the center hole 51 in the filter 43 substantially to the bottom of the hemispherical lower end 35 of the vessel 33. The hole 51 may be of substantially larger diameter than the leg, and the latter may be sealed in the hole by a suitable sealant, such as silicone rubber as indicated at 61.

The supply or charge 3 of the parent radioisotope is packed in the vessel above the filter and surrounds the vertical leg 55 of the tubing 53, which leg extends down generally centrally of the vessel. The charge 3 comprises the parent radioisotope adsorbed on an anion exchange medium, alumina or other suitable medium, in granular form, and having under suitable conditions, a high adsorption capacity or affinity for the parent radioisotope but a low adsorption capacity for the daughter radioisotope. For generation of technetium- 99m, for example, the charge 3 in the vessel may comprise molybdenum-99, in the form of ammonium molybdate, as the parent radioisotope, adsorbed on alumina, the latter constituting a medium having a high adsorption capacity for ammonium molybdate Mo-99 but a low adsorption capacity for the daughter technetium-99m compound in the presence of certain known eluting solutions.

The eluant conduit 9 comprises a length of relatively small diameter metal tubing 63 (e.g., stainless steel tubing) like tubing 53, bent to have a relatively short vertical leg 65 and a horizontal arm 67. The lower end of the vertical leg is beveled as indicated at 69. The vertical leg 65 extends down through the stopper 39, its beveled lower end 69 permitting it to be pierced through the stopper, and terminates just below the stopper. The charge 3 substantially fills the vessel from filter 43 up to the stopper, and leg 65 may reach down just into the top of the charge. The eluant conduit 9 further comprises a length of flexible tubing 71 interconnecting the eluant supply means 7 and a fitting 73 on the end of the arm 67 of tubing 63. As herein shown, the eluant supply means 7 comprises a plastic bag or transfer pack containing the eluant, this bag being subject to being squeezed by atmospheric pressure, the bag having an outlet 75 from which flexible tubing 71 extends to the fitting 73 on the end of arm 67. The eluant may be, for example, a sterile pyrogen-free saline solution which in the case of elution of technetium-99m as the daughter radioisotope from molybdenum-99, results in the daughter radioisotope being present in the eluate as sodium pertechnetate.

As herein illustrated, the shield 5 for the generator comprises a relatively thick-walled receptacle, which may be made of lead or other suitable shielding material, formed to provide a cylindric chamber 77 extending down from the top of the receptacle, and formed with supporting legs 79. Chamber 77 has a diameter somewhat greater than that of the generator 1 and a length (height) somewhat greater than that of the generator. The receptacle is formed with two diametrically opposite slots 81 extending down from its upper end, and is closed, after insertion of the generator therein, by a closure constituted by a plug 83 made of lead or other suitable shielding material inserted in the upper end of the chamber. The generator is inserted in the chamber with arms 57 and 67 of the metal tubing portions 53 and 63 of the eluant and eluate conduits 9 and 27 extending laterally outward through the slots 81 at the lower ends of those slots (the generator, in effect, being hung in the chamber by engagement of arms 57 and 67 with the lower ends of the slots). The plug has two ears 85 extending outward therefrom diametrically opposite one another fitting in the slots and bearing on the arms. The plug may be removably secured to the receptacle (after insertion of the generator) as byadhesive tape (not shown) or in any other suitable manner.

The shield 5 with the generator 1 sealed therein and the plastic bag 7 containing the eluant are supplied in a case generally designated 87. This case, which may be made of either transparent or opaque plastic or any other suitable material, comprises a bottom section 89 and a cover 91. The bottom section 89 has a circular flat bottom plate 93, an internal cylindric wall 95 extending up from bottom 93 and concentric therewith, and an external peripheral wall 97 extending up from the margin of bottom 93. Wall 97 is part cylindric, having a gap 99 therein spanning somewhat less than 90 of arc. Radial partitions 101 and 103 extend from the internal wall 95 to the peripheral wall 97, the outer ends of these partitions (which lie in planes at right angles to one another) being joined to the peripheral wall 97 on opposite sides of the gap 99. Partitions 105 and 107 extend from the internal wall 95 to the peripheral wall 97 diametrically opposite partitions 101 and 103. A curved panel 109, convexly curved as viewed from outside the case, extends between the vertical margins of the peripheral wall 97 on opposite sides of the gap 99 in wall 97 and butts against the internal wall 95. This curved panel defines a recess 111 opening inward from the respective side of the case, bottomed by portion 93a of the bottom plate.

The walls 95 and 97 and partitions 101, 103, 105 and 107 are of equal height, somewhat less than the height of the shield 5. The curved panel 109 has an upward extension 113 of reduced width extending up above the level of the top of walls 95 and 97 and the partitions. The top of the recess 1 1 1 is closed by a horizontal head plate 115 at the top of extension 113, this plate 115 having an inner edge curved in correspondence with the curvature of the panel, and an outer edge 117 curved on an are centered in the vertical central axis of the case bottom section 89 of radius corresponding to the radius of the inside of the peripheral wall 97. Plate 115 has a centrally located vertical opening 119 and an annular boss 121 extending upward around this openmg.

The internal wall 95 has an internal diameter somewhat larger than the cross section of shield 5 and defines a chamber 123 located centrally of the case bottom section 89 receiving the shield. The feet of the latter are confined within a centering ring 125 projecting up from bottom 93 of section 89 within the wall 95. Partitions 105 and 107 in conjunction with walls 95 and 97 define a compartment 127 receiving the plastic eluant bag 7.

The cover 91 comprises a cylindric external peripheral wall 129 having the same diameter as wall 97, and a cylindric internal wall 131 having the same diameter as wall 95. Radial partitions 133, 135, 137 and 139 (corresponding to partitions 101, 103, 105 and 107) extend between these walls. The upper rims of walls 129 and 131 are at the same level, but wall 129 extends down somewhat farther than wall 131. Wall 129 has a relatively wide shallow notch 141 in its lower margin, the width of this notch corresponding to the width of gap 99. Extending around the inside of wall 129 at the lower end thereof from adjacent one side of the notch to the other is a rim 143 which projects down below the lower edge of wall 129 an which has a telescopic sliding fit within wall 97 of the case bottom section 89. The downwardly projecting portion of this rim has notches 145 receiving the partitions 103, 105, 107 and 109. Wall 131 defines a chamber 146 for the upper end of shield 5, and has notches 147 at its lower end for passage of arms 57 and 67. Chamber 146 is closed at the top by a circular top plate 149 spaced somewhat below the upper end of wall 131 to provide a circular compartment 151 for holding a supply of needles 13. A plate 153 closes the top of the space bounded by partitions 133 and 135 and walls 129 and 131, and a plate 155 closes the top of the space bounded by partitions 137 and 139 and walls 129 and 131, defining oppositely located downwardly opening chambers 157 and 159. Plates 161 close the bottom of the space bounded by partitions 133 and 139 and the bottom of the space bounded by partitions 135 and l37'and walls 129 and 131, defining two oppositely located upwardly opening compartments 163 for holding a supply of evacuated bottles 15.

The means 25 for mounting the tubular fitting 11 includes a tubular plunger 165 mounted for vertical sliding movement in the opening 119 in the plate 115 and in an aligned opening 167 in the plate 153 of the cover, these plates constituting a portion of the case 87 overhanging the recess lll. An annular boss 169 extends down from plate 153 around the opening 167, and has an annular groove 171 of inverted V-section in its lower end. The plunger has a plug 173 in its lower end, the fitting 11 being received in an axial opening 175 in the plug. The fitting extends down from the plug for attachment of the needle 13 to the lower end of the fitting with the needle extending downward from the lower end of the fitting by applying a ferrule 177 on the upper end of the needle to the lower end of the fitting. The plunger has a lateral opening 179 (see FIG. 7) spaced from its lower end located between the plates 115 and 153. The flexible tubing portion 29 of the eluate conduit 27 extends through this opening and down through the plunger to a connection at 181 with the upper end of fitting 11. The plunger has an annular collar 183 thereon immediately below the opening 179 fonned with an upwardly extending annular rib 185 of inverted V-section matching the V-section groove 171 in boss 169. A coil compression spring 187 surrounding the plunger reacts from the boss 121 against the collar 183 to bias the plunger upward toward its raised retracted position in which it is illustrated in FIG. 4. A knob 189 is provided at the upper end of the plunger. Axially extending keys 191 on the plunger slide in keyways 193 at opposite sides of opening 167 to prevent rotation of the plunger about its vertical axis.

The collar 183 on the plunger 165 constitutes a movable jaw member which functions in conjunction with boss 169 as a fixed jaw member topinch closed the flexible tubing portion 29 of the eluate conduit where it extends into the opening 179 when the plunger is biased upward to its raised retracted position by the spring 187 (see FIGS. 1, 3 and 4). The latter exerts sufficient upward force on the plunger for this purpose. When the plunger is driven downward against the return bias of spring 187, the pinch of the tubing por tion 29 is released and the eluate conduit is thus opened for flow of eluate.

In manufacturing the generator of the invention, cylindric vessel 33 is first provided with fritted glass filter 43 as described above. The center hole 51 in the filter is then covered with a material such as a silicone rubber compound which is allowed (i.e., cure. The rubber stopper 39 is next plugged into the neck of vessel 33, and eluate conduit 27 (i.e., tubing 53) is inserted through stopper 39 and hole 51 and sealed into the lower end of vessel 33 with its beveled end 59 in the position shown in F IG. 8. Stopper 39 is then pushed up without moving conduit 27 so as to permit loading of the alumina substrate into vessel 33 through its open top. The stopper is thereafter pushed down and the aluminum foil cover 41 crimped onto the top of vessel 33. The eluant conduit 9 (i.e., tubing 63) is inserted through stopper 39 to complete the assembly of the generator. An acid solution, for example 0.1N hydrochloric acid, is then introduced into the generator through eluant conduit 9 and withdrawn through eluate 27, after which a radioactive ammonium molybdate solution is introduced into the generator through eluant conduit 9 for adsorption onto the alumina to form the supply 3 of parent radioisotope, The parent radioisotope may be washed with hydrochloric acid introduced through eluant conduit 9 and withdrawn through eluate conduit 27 prior to sterilizing the generator as by autoclaving.

The generator 1, containing the sterile pyrogen-free supply 3 of the parent radioisotope, and itself being made sterile and pyrogen-free (as by heating) is placed in chamber 77 in the lead shield 5, and the latter is closed by the plug 83. The shield 5 and the plastic bag 7 containing the supply of sterile pyrogen-free eluant are placed in the bottom section 89 of the case 87, tubing 71 is connected to fitting 73, and tubing 29, extending from fitting 11 out of the plunger 165 through opening 179, is connected to a fitting 195 on the end of arm 57. The metal'tubing and flexible tubing portions of the eluant and eluate conduits and fitting 11 are all in sterile and pyrogen-free condition, and it will be understood that the needles 13 are supplied in sterile pyrogen-free condition. The cover 91 of the case 87 is applied to the bottom section 89, and secured thereto in any suitable manner, as by adhesive tape, or by use of a solvent for the plastic of the case and cover to cause them to become bonded together. The containers or vials 15, as initially supplied, are sterile and pyrogen-free and evacuated of air. They may have graduations marked thereon for indicating volume of eluate drawn thereinto.

In the use of the apparatus, an evacuated container or via] 15, held in a lead cup 197, is placed in the recess 1 ll of the case 87 with the stopper 19 of the vial in line with the needle 13 on the lower end of the fitting 11. The plunger 165 is then manually pushed downward against the upward return bias of spring 187 to cause the needle 13 to pierce through the stopper 19 of the vial (see FIG. 7) and simultaneously to effect release of the flexible tubing portion 29 of the eluate conduit 27 by the jaw member 183 so as to open the eluate conduit. This results in suctioning of the eluant from the eluant supply bag 7 (which is under atmospheric pressure) through the eluant conduit 9 into the generator 1 for eluting the daughter radioisotope from the parent radioisotope in the generator. The resultant eluate passes down through the filter 43 into the eluate chamber 49 at the lower end of the generator, and is suctioned upward through leg 55 of metal tubing 53 and thence through flexible tubing portion 29 of the eluate conduit 27, and fitting l1 and needle 13 into the evacuated vial IS.- The plunger is held down until the desired amount of eluate has been suctioned into the vial, and then released to be returned to its raised retracted position by the spring 187, resulting in pinching of the flexible tubing portion 29 of the eluate conduit 27 to cut off further flow as might otherwise occur due to siphoning action. The filled vial is then taken away for ultimate use, and the apparatus is ready for the next milking operation.

It will be observed that the milking operation is carried out without opening of the shield 5, hence does not involve any exposure of the operator to radiation from the generator 1. The latter at all times remains essentially sealed within the shield, which is made of lead or other suitable material for shielding against radioactive emission from the generator. After the first milking operation, there will be some eluant in the eluant conduit 27 from the shield to where the flexible tubing portion 29 of the eluant conduit is pinched between jaw members 183 and 169, but radiation from this amount of eluant is minor.

While, as above described, the elution is by use of an evacuated container 15 and suctioning of the eluant into the generator and the eluate out of the generator (i.e., a vacuum system), the principles of the invention are also applicable to a pressure system, as distinguished from a vacuum system, using a nonevacuated container or vial, and in which the eluant supply would be under pressure above atmospheric pressure .or adapted for flow by gravity through the generator into the vial, and a vent would be provided in the stopper of the vial.

As can be seen from the above, the provision of a vessel integrally closed at one end eliminates one stopper closure and hence one possible source of leaks of radioactive solution from the generator. The generator of the invention also eliminates one possible source for loss of sterility of the system. Further, the arrangement of the eluant and eluate conduits, even if not connected to a completely closed system as described above reduces the amount of handling necessary in using the apparatus.

Similarly, although the vessel has been described above as vertically disposed with its open end up, it should be apparent that other orientations of the vessel are possible and within the scope of the instant inventron.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous' results attained.

As various changes could be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

What is claimed is:

l. A generator for eluting a daughter radioisotope from a parent radioisotope comprising an elongate closed vessel having an integral convergent closed lower end and containing therein a supply of a parent radioisotope, means in said vessel spaced from the lower end thereof for maintaining the supply of the parent radioisotope spaced from said lower end, a closure for the upper end of said vessel, a first conduit extending through said closure and communicating with the upper end of the vessel for introducing an eluant into the vessel and a second conduit extending through said closure and said supply and said means and communicating with the lower end of the vessel for passage of eluate from the lower end of the vessel.

2. A generator according to claim 1, characterized in that the vessel comprises a glass tube having a hemispherical lower end, the closure comprises a stopper in the upper end of the tube, the means for maintaining the parent radioisotope spaced from its lower end comprising a filter mounted in the tube above its lower end, the parent radioisotope being confined between the filter and the stopper, the first conduit extending down through the stopper and terminating immediately below the stopper, the second conduit extending down through the stopper and the filter to the lower end of the tube. 

1. A generator for eluting a daughter radioisotope from a parent radioisotope comprising an elongate closed vessel having an integral convergent closed lower end and containing therein a supply of a parent radioisotope, means in said vessel spaced from the lower end thereof for maintaining the supply of the parent radioisotope spaced from said lower end, a closure for the upper end of said vessel, a first conduit extending through said closure and communicating with the upper end of the vessel for introducing an eluant into the vessel and a second conduit extending through said closure and said supply and said means and communicating with the lower end of the vessel for passage of eluate from the lower end of the vessel.
 2. A generator according to claim 1, characterized in that the vessel comprises a glass tube having a hemispherical lower end, the closure comprises a stopper in the upper end of the tube, the means for maintaining the parent radioisotope spaced from its lower end comprising a filter mounted in the tube above its lower end, the parent radioisotope being confined between the filter and the stopper, the first conduit extending down through the stopper and terminating immediately below the stopper, the second conduit extending down through the stopper and the filter to the lower end of the tube. 